In this application, we propose to study behavioral profiles and genetic bases of severe reading impairment.[unreadable] Specifically, we will establish a unique sample of 500 severely affected elementary schools children[unreadable] ascertained through the PMRN database and will then recruit at least two first-degree relatives of the[unreadable] probands for a sample of approximately 1,500 individuals. We will administer a comprehensive behavioral assessment to[unreadable] all elementary school children and collect DNA samples from all participants. The behavioral phenotypes will[unreadable] be comprehensively studied, both cross-sectionally and longitudinally. In addition, we propose to conduct a[unreadable] relatively narrowly targeted, but in-depth, molecular-genetic study of Specific Reading Disability (SRD).[unreadable] Specifically, we aim to evaluate, in the newly collected PMRN database samples, the association between[unreadable] specific candidate genes and SRD. We propose to begin this work with a gene currently under examination,[unreadable] KIAA0319, and anticipate that during the life of this project there will be other candidate genes put forward[unreadable] through the efforts of different research groups around the world. In investigating these associations, we[unreadable] propose to crystallize a data-analytic approach that permits simultaneous analyses of multivariate[unreadable] phenotypes and multiple QTLs both cross-sectionally and longitudinally. In addition, although relatively small[unreadable] in magnitude, this study will offer a unique prospective on the contribution of each of the candidate genes by[unreadable] considering identified risk and/or protective alleles and risk and/or protective haplotypes in global genetic[unreadable] variation and evolutionary contexts. Specifically, the candidate genes will be investigated for ancestral alleles[unreadable] and haplotypes and global variation of allele and haplotype frequencies in samples from 38 world[unreadable] populations and a number of primate species. This in-depth analysis will permit evaluation of the frequency[unreadable] and structure of the candidate genes' haplotype around the world and, therefore, will increase the[unreadable] generalizability of results indicating the presence of association. In summary, we propose to combine[unreadable] behavior analyses and statistical, molecular, and population genetics in an attempt to understand[unreadable] associations between specific candidate genes and multiple facets of SRD in a unique, phenotypically[unreadable] informative, large sample of trios of first-degree relatives ascertained through probands whose severity of[unreadable] reading impairment puts their performance below the 3rd percentile on indicators of single-word processing.[unreadable]